This section introduces aspects that may help facilitate a better understanding of the disclosure. Accordingly, these statements are to be read in this light and are not to be understood as admissions about what is or is not prior art.
Chiral boronic acids and their derivatives are highly versatile building blocks in modern asymmetric synthesis. Their stereospecific conversion into a broad range of useful functional groups is a continually growing and important research area. Additionally, many unique biological activities of boron-containing compounds have been revealed. Among them, chiral α(alfa)-aminoboronic acids have received significant attention since they are the key pharmacophores in protease inhibitions such as Bortezomib (Velcade, an anti-cancer drug and the first therapeutic proteasome inhibitor) and Ixazomib (Ninlaro, a drug for the treatment of multiple myeloma). In addition, many other α-aminoboronic acid compounds showed excellent anticancer, antiviral, and antibacterial activities. From the success of these compounds, there has been an increased interest in searching α-amino boronate-containing small bioactive molecules (FIG. 1).

In view of their broad biological activities, substantial efforts have been made to develop synthetic methods for the asymmetric construction of α-aminoboronic acids and their derivatives. Previous approaches by either use of chiral auxiliaries or asymmetric catalytic transformations have been utilized for the efficient preparation of a variety of α-aminoboronic acid derivatives, whereas they mainly limited to the construction of chiral α-amino secondary boronic esters.
Indeed, there have been only a limited number of reports on asymmetric approaches to more sterically congested α-amino tertiary boronic esters, which involves a particular challenge for the stereoselective construction of N-substituted quaternary carbon stereogenic centers (Scheme 1). For example, significant lower enantioselectivity was observed for the synthesis sterically hindered α-amino tertiary boronic esters compared to secondary boronic esters by borylation of imines and Cu-catalyzed hydroamination of alkenyl dan-boronates. Recently, Ellman reported a copper-catalyzed diastereoselective borylation of chiral N-tert-butanesufinyl ketimines with involvement of a chiral auxiliary (Scheme 1, eq 1). See A. W. Buesking, V. Bacauanu, I. Cai, J. A. Ellman, J. Org. Chem. 2014, 79, 3671-3677. In another approach, Tang described an elegant enantiospecific synthesis of N-substituted quaternary α-aminoboronic esters by rhodium-catalyzed hydroboration of α-arylenamides (Scheme 1, eq 2). See N. Hu, G. Zhao, Y. Zhang, X. Liu, G. Li, W. Tang, J. Am. Chem. Soc. 2015, 137, 6746-6749. Very recently, Ready and Studer developed transition-metal catalyzed enantiospecific and diastereoselective multi-component coupling involving indolylboron ate complexes to provide α-substituted indoline boronic esters, respectively (Scheme 1, eq 3 and eq 4). See S. Panda, J. M. Ready, J. Am. Chem. Soc. 2017, 139, 6038-6041; b) S. Das, C. G. Daniliuc, A. Studer, Angew. Chem. Int. Ed. 2018, 57, 4053-4057.

Despite recent progress, there remains a great challenge for the synthesis of N-substituted quaternary α-aminoboronic esters with high enantiopurity in a general manner.